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Cancer associated talin point mutations disorganise cell adhesion and migration

Azizi, Latifeh, Cowell, Alana R, Mykuliak, Vasyl V, Goult, Benjamin T, Turkki, Paula, Hytönen, Vesa P (2021) Cancer associated talin point mutations disorganise cell adhesion and migration. Scientific Reports, . ISSN 2045-2322. (doi:10.1038/s41598-020-77911-4) (KAR id:80675)

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https://doi.org/10.1038/s41598-020-77911-4

Abstract

Talin-1 is a key component of the multiprotein adhesion complexes which mediate cell migration, adhesion and integrin signalling and has been linked to cancer in several studies. We analysed talin-1 mutations reported in the Catalogue of Somatic Mutations in Cancer database and developed a bioinformatics pipeline to predict the severity of each mutation. These predictions were then assessed using biochemistry and cell biology experiments. With this approach we were able to identify several talin-1 mutations affecting integrin activity, actin recruitment and Deleted in Liver Cancer 1 localization. We explored potential changes in talin-1 signalling responses by assessing impact on migration, invasion and proliferation. Altogether, this study describes a pipeline approach of experiments for crude characterization of talin-1 mutants in order to evaluate their functional effects and potential pathogenicity. Our findings suggest that cancer related point mutations in talin-1 can affect cell behaviour and so may contribute to cancer progression.

Item Type: Article
DOI/Identification number: 10.1038/s41598-020-77911-4
Uncontrolled keywords: talin, COSMIC, somatic mutations, cancer, migration, invasion, focal adhesion
Subjects: Q Science > QH Natural history > QH581.2 Cell Biology
Divisions: Divisions > Division of Natural Sciences > School of Biosciences
Depositing User: Ben Goult
Date Deposited: 31 Mar 2020 13:50 UTC
Last Modified: 12 Jan 2021 14:03 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/80675 (The current URI for this page, for reference purposes)
Goult, Benjamin T: https://orcid.org/0000-0002-3438-2807
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